Forty percent of the neurons in the superior cervical sympathetic ganglion (SCG) degenerate during the first postnatal week of normal development in the rat. The number of neurons in the SCG that survive beyond this first week can be dramatically enhanced by treatment with exogenous estradiol or testosterone beginning shorlty after birth. The developmental mechanism underlying this gonadal steroid induced regulation of neuron survival is not known. Specific binding of both estradiol and testosterone have been found in cytosol fraction of SCGs from adult female rats. However, it is not known whether this binding is to neurons or non-neuronal cells within the ganglion. Neither is it known whether this binding is present in the SCGs of neonates when exposure to these hormones enhances SCG neuron survival, and if so, whether this ganglionic binding of steroids the increased neuronal survival. The proposed experiments will use autoradiographic techniques to localize estrogen binding within the SCG of the rat. Another set of studies will determine whether testosterone, estradiol or dihydrotestosterone enhance the viability of growth of SCG neurons, in culture, either by direct action on neurons, or via action on Schwann cells. These studies will use cultures of SCG neurons alone or in combination with Schwann cells grown in a serum-free, defined medium. The gonadal steroids could also increase neuron numbers by prolonging proliferation, either of neurons directly, or by increasing numbers of non-neuronal cells before or during normal neuron death, when their presence could enhance the number of neurons that survive. These questions will be addressed using thymidine autoradiography. The proposed studies will determine which cells within the SCG bind estrogen, and whether gonadal steroids act directly on these cells to increase survival or stimulate neurite outgrowth that could secondarily result in increased survival of SCG neurons in vivo, or whether proliferation on non-neuronal cells are involved in the gonadal steroid regulation of neuronal survival. These results will be important to understanding the regulation of neuron degeneration that may be related to pathological neuronal degeneration, as well the development of normal sex differences.